Abstract Body (Do not enter title and authors here): Introduction: Although coronary endothelial dysfunction is thought to affect coronary atherothrombogenic processes, there has been little practical evidence for the relationship between clinical evolution of fatal or non-fatal acute coronary syndrome and coronary endothelial dysfunction.
Hypothesis: We assessed hypothesis that coronary endothelial dysfunction has clinical impacts on development of acute coronary syndrome and fatal cardiovascular events.
Methods: Coronary endothelial dysfunction was practically graded by the flow-mediated endothelium-dependent reactive changes in coronary artery diameter (CFMD) to infusion of adenosine triphosphate (ATP ; 50μg) into the normal left coronary artery using quantitative coronary arteriography in 150 patients with stable coronary artery disease. The enrolled patients were categorized into tertile groups according to the values of CFMD, and we prospectively followed-up major adverse clinical cardiac events including acute coronary syndrome and cardiovascular death.
Results: For a mean follow-up period of 132 months (range; 120 to 144) with complete follow-up, the patients in the lower third with severe coronary endothelial dysfunction (Group-L) more frequently developed acute coronary syndrome than those in the middle third with mild coronary endothelial dysfunction (Group-M) plus those in the higher third without coronary endothelial dysfunction (Group-H) [Group-L versus Group-M plus Group-H: 15(30%) versus 5(10%) plus 0(0%), p<0.001, by Kaplan-Meier analysis]. Majority of the patients who resulted in cardiovascular death belonged to Group-L, [6(12%) versus 1(2%) plus 0(0%), p=0.014, by Kaplan-Meier analysis]. Cox hazard proportional model analyses including clinical and angiographical variables indicated that severe coronary endothelial dysfunction was the strong predictor for future acute coronary syndrome (hazard ratio=7.53, 95%confidential interval; 1.78-12.25, p<0.001) and future cardiovascular death (hazard ratio=13.50, 95%confidential interval; 1.55-25.25, p=0.005).
Conclusions: This is the novel and longest follow-up investigation that demonstrates coronary endothelial dysfunction plays important roles on development of acute coronary syndrome and fatal cardiovascular events and therefore the strategies based on practical status of coronary endothelial dysfunction are required to prevent major adverse ischemic cardiac events.